The aim of the proposed activity will be to develop a book that selects, describes, and documents the impact of the most important randomized clinical trials (RCTs) in all areas of medicine and public health since 1948, the year of the first large-scale RCT in medicine, the British Streptomycin trial. Surprisingly, in spite of the recognized importance of RCTs for the practice of medicine, no such source currently exists. This will be an edited book, and will be the main product of an organizational effort called Project ImpACT (Important achievements of Clinical Trials). This project will involve a range of clinical researchers, specialists, and (knowledgeable methodological experts from all domains of medicine. We are defining "impact" very broadly, as: 1.) Impact on the practice of medicine or public health (e.g. therapies or practices started or stopped on the basis of an RCT.) 2.) Impact on methods of designing, conducting or analyzing trials. (e.g. stimulating recognition of the need for data monitoring boards) 3). Impact on the subsequent course of research. 4.) Impact on the understanding of pathophysiology and biology. 5.) Impact on regulations, law or policy 5.) Impact on ethical understanding and conduct of trials In addition to reporting the design and findings of the included trials, this book will attempt to describe what cannot typically be found in published trial reports; the state of knowledge or practice before the trial was reported, the political and scientific context in which the trial was developed, the various design choices that the investigators considered and the battles that may have been fought to get the trial designed the way it was, the reasons it had an impact where previous trials may not have, and the nature of the immediate and longer term reactions to the trial conduct or results. This information will be gathered from ancillary articles written about the trial by either the participating investigators or others, editorials, textbooks, and accounts of historians, scholars and journalists. This will be augmented where possible by information from specialists in the field, from the investigators themselves, and from scientists who were active during the time of the trial. The ultimate goal will be to learn from these trials in a way that will teach us lessons that are relevant to present struggles and tough questions, and be informative and interesting to clinicians, medical researchers, methodologists and policy makers.